Rosiglitazone modifies the adipogenic potential of human muscle satellite cells.

Abstract:

AIMS/HYPOTHESIS:Satellite cells are responsible for postnatal skeletal muscle regeneration. It has been demonstrated that mouse satellite cells behave as multipotent stem cells. We studied the differentiation capacities of human satellite cells and evaluated the effect of the insulin sensitiser rosiglitazone, a well known peroxisome proliferative activated receptor gamma (PPARG) agonist, on their adipogenic conversion. SUBJECTS, MATERIALS AND METHODS:We obtained human satellite cells from human muscle biopsies of healthy subjects by single-fibre isolation and cultured them under myogenic, osteogenic and adipogenic conditions. Moreover, we compared the morphological features and the adipose-specific gene expression profiling, as assessed by quantitative PCR, between adipocytes differentiated from human satellite cells and those obtained from the stromal vascular fraction of human visceral fat. RESULTS:We proved by morphological analysis, mRNA expression and immunohistochemistry that human satellite cells are able to differentiate into myotubes, adipocytes and osteocytes. The addition of rosiglitazone to the adipogenic medium strongly activated PPARG expression and enhanced adipogenesis in human satellite cells, but did not in itself trigger the complete adipogenic programme. Moreover, we observed a decrease in wingless-type MMTV integration site family member 10B and an upregulation of growth differentiation factor 8 expression, both being independent of PPARG activation. CONCLUSIONS/INTERPRETATION:Human satellite cells possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle in pathological conditions such as obesity, type 2 diabetes and ageing-related sarcopenia. Rosiglitazone treatment, while enhancing adipogenesis, induces a more favourable pattern of adipocytokine expression in satellite-derived fat cells. This could partially counteract the worsening effect of intermuscular adipose tissue depots on muscle insulin sensitivity.

journal_name

Diabetologia

journal_title

Diabetologia

authors

De Coppi P,Milan G,Scarda A,Boldrin L,Centobene C,Piccoli M,Pozzobon M,Pilon C,Pagano C,Gamba P,Vettor R

doi

10.1007/s00125-006-0304-6

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

1962-73

issue

8

eissn

0012-186X

issn

1432-0428

journal_volume

49

pub_type

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